Sulfonyl hydrazides as a general redox-neutral platform for radical cross-coupling.

Sun, Jiawei; Péter, Áron; He, Jiayan; Tsien, Jet; Zhang, Haoxiang; Cagan, David A; Vokits, Benjamin P; Peters, David S et al. · Science · 2025

basic_science · Level V

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Abstract

Sulfonyl hydrazides are stable and usually crystalline substances that can be accessed in a variety of ways, including transiently from hydrazones, to achieve a net reductive arylation of carbonyl compounds. We show their utility as versatile radical precursors, as exemplified with seven C-C bond-forming, redox-neutral cross-couplings with activated olefins, alkyl halides, redox-active esters, aryl halides, alkenyl halides, alkynyl halides, and a trifluoromethylating reagent, to forge C(sp<sup>3</sup>)-C(sp<sup>3</sup>), C(sp<sup>3</sup>)-C(sp<sup>2</sup>), and C(sp<sup>3</sup>)-C(sp) bonds. Exogenous redox (chemical, photo/electrochemical) additives are not necessary because these functional groups serve the dual role of radical precursor and electron donor. The homogeneous, water-compatible reaction conditions are operationally simple and contribute to streamlining synthesis and mild late-stage functionalization.